The acquired immunodeficiency syndrome (AIDS) is a global pandemic with over 11 million HIV-infected individuals worldwide. A major focus within our laboratory has been on defining the unique epidemiologic, clinical, virologic and immunologic features of HIV-1 and HIV-2 infections in developing countries and in the U.S. In Port-au-Prince, Haiti, we demonstrated that nearly 10% of pregnant women are currently HIV-infected and have a 2% annual seroincidence. In a survey in Kinshasa, Zaire, we demonstrated a 40% infection rate in female prostitutes with an estimated 10% annual seroincidence. Among patients attending STD clinics in Baltimore, a retrospective 10-year survey demonstrated a marked increase in HIV infection to 5.5% with a current annual seroincidence of 2.0%. Common to all three cohorts was the strong association of HIV infection among heterosexuals with past or active genital ulcerative and non-ulcerative STDs, smoking, lack of circumcision, and inconsistent use of condoms. We have documented a 28% perinatal transmission rate with transmission associated with depressed maternal CD4+ lymphocyte counts, anemia, chorioamnionitis and funisitis. There was no association between the presence of neutralizing antibodies to the V3 loop of gpl20 and perinatal transmission. Following acid association of immune complexes, we were able to demonstrate extremely high levels of p24 antigenemia during the first three months of life in perinatally infected children. When used in combination with either PCR or an IqA assay for HIV-specific antibodies, the diagnosis of perinatal HIV infection could be established within the first three months of life with a sensitivity and specificity of 99%, respectively. The identification of CD4+ and CD8+ CTL clones in volunteers receiving recombinant gp160 vaccines led to the recognition that upon antigen stimulation, these clones were capable of producing high levels of TNF-alpha which resulted in up-regulation of HIV in latently infected cell lines. Additional studies are planned to further elucidate the elaboration and importance of these CTL clones in the immune response to HIV infection.